The objectives of the proposed research are (1) to investigate the mechanisms involved in the compensatory response (sometimes called intestinal adaptation) of the intestine after the ileum and/or jejunum are subjected to various proliferative stimuli and (2) to provide a biological and biochemical basis for the responses involved as they relate to the control or regulation of intestinal cell proliferation. The responses of portions of the intestine to a number of stimuli including X-irradiation, resection, split courses of resection only, radiation and resection, intestinal ischemia and resection will be documented and quantified. The magnitude, the time of earliest appearance, and the sequence of changes will be studied not only in the intestinal region most directly affected by the treatment employed, but also in more remote, uninjured sites of the gastrointestinal tract. The biological parameters of the intestinal response which will be measured include determination of crypt depth and height, labeling index, mitotic index, frequency and type of crypt bifurcation (fission), and tritiated thymidine uptake per crypt. Cyclic AMP levels are thought by some to reflect the state of proliferation in cell renewal systems. Since some of our studies with induction of the compensatory response have shown that cAMP levels are altered and therefore reinforced this contention, it seems necessary to continue the study of the biochemical basis for the biologic responses observed. To accomplish this end, whole tissue slices and isolated villus or crypt cell preparations will be taken from rats at the time of sacrifice and utilized for various biochemical analyses. The concentrations of cAMP, Types I and II protein kinase, the responsiveness of adenylate cyclase to various chemical stimuli, and levels of cAMP phosphodiesterase will be measured. The results should help provide a mechanism(s) for the expression of biologic control of cell proliferation after resection and/or X-irradiation.